Protein folding is the process by which a protein acquires its native three-dimensional functional structure. Some proteins, however, cannot achieve this state and may become toxic or cause serious diseases. Techniques like differential scanning fluorimetry and the modified nanoDSF methods can be used to characterize protein unfolding through thermal and chemical denaturation studies. Measuring results for any protein type has become very useful for understanding protein behavior.
nanoDSF
Recently developed methods, such asnanoDSF, allow researchers to produce uncompromising results by screening the thermal stability of globular proteins without using aggregates in solution. This method produces accurate measurements of protein unfolding temperatures, free folding energy and aggregation results. Furthermore, nanoDSF utilizes low sample consumption allowing laboratories to predict even the most subtle protein misfolding and consequent aggregation. By screening precisely for buffer influences, or testing formulation and storage conditions, researchers can make better decisions based on complete results.
Accurate results provide crucial information for better predicting protein stability, protein development, and long-term storage of antibody candidates (1) that can be very useful for understanding diseases and developmenting drugs to treat them.
Understanding Protein Structure
Protein function is dictated by the primary amino acid sequence, which determines the three-dimensional structural organization and dynamic behavior of proteins (2). Through evolution, proteins have achieved a fine balance between thermodynamic stability and dynamic fluctuations to optimally perform their biological functions in the environmental setting of their host (3). Studies show that misfolding or failure to fold into native structure produces inactive proteins in almost all cases. In some instances, however, misfolded proteins can have a modified or toxic functionality. This can be due to unwanted mutations in the amino acid sequence, or errors in the folding process (4).
An accumulation of misfolded proteins can affect our central nervous system and cause a class of diseases known as amyloid diseases. Alzheimer’s disease, the 6th leading cause of death in the United States (5), is one example of amyloid disease. Parkinson’s disease and Huntington’s disease are other examples, for which our risk of disease development increases with age. Protein aggregation can also affect our peripheral tissues, causing amyloidogenic diseases such as Type 2 Diabetes and some forms of Atherosclerosis.
Our cells have mechanisms to prevent proteins from misfolding, which take the form of chaperones. These biomolecules, under normal circumstances, assist proteins in proper assembly and folding. In spite of chaperone actions, some proteins still misfold due primarily to cell mutations. Additionally, as we age, chaperone regulatory systems begin to fail. When this happens, disorders in protein stability and folding begin to occur due to improper degradation, mislocalization, dominant-negative mutations, structural alterations that establish novel toxic functions, and amyloid accumulation (6). Consequently, accurate protein characterization technologies are crucial for early disease detection as well as the development of better disease treatments.
Many disease treatment therapies use chaperones or seek to correct specific regulatory protein folding networks. Although there have been serious improvements in the field, the road to understanding how protein pathways operate is a long one. nanoDSF technology helps to explore protein folding in both pathological and nonpathological states, which sheds a new light on the best way to develop more innovative treatments.
Sources:
- https://nanotempertech.com/prometheus/
- Mitrea D., Kriwacki R. Regulated Unfolding of Proteins in Signaling. FEBS Lett. 2013 Apr 17; 587(8): 1081–1088.Published online 2013 Feb 20. doi: 10.1016/j.febslet.2013.02.024
- Feller G. Protein stability and enzyme activity at extreme biological temperatures. Journal of physics Condensed matter: an Institute of Physics journal. 2010;22:323101.
- Chaudhuri TK, Paul S (April 2006). “Protein-misfolding diseases and chaperone-based therapeutic approaches”. The FEBS Journal. 273 (7): 1331–49. PMID 16689923. doi:10.1111/j.1742-4658.2006.05181
- http://www.alz.org/facts/
- Valatyan J., Lindquist S. Mechanisms of protein-folding diseases at a glance. Dis Model Mech. 2014 Jan; 7(1): 9–14. doi: 10.1242/dmm.013474.
Author’s Bio
Judy lees is a super-connector with AYC Web Solutions who helps businesses find their audience online through outreach, partnerships, and networking. She frequently writes about the latest advancements in digital marketing and focuses her efforts on developing customized blogger outreach plans depending on the industry and competition.
